Snail and SIP1 increase cancer invasion by upregulating MMP family in hepatocellular carcinoma cells.
Snail and SIP1 increase cancer invasion by upregulating MMP family in hepatocellular carcinoma cells.
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DOI：
10.1038/sj.bjc.6601685
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发表时间：
2004-03-22
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
E-钙粘蛋白（E-cad）的丢失触发各种上皮癌的侵袭、转移和去分化。最近有报道称，两种转录因子Snail和SIP 1（Smad interacting protein 1）通过结合E-cad启动子上的E-box直接抑制E-cad基因的转录。我们的目的是研究Snail和SIP 1在肝细胞癌（HCC）中的分子机制。我们首先发现E-cad和Snail/SIP 1表达在5个不同表型的肝癌细胞系中呈负相关。结果表明，未分化型，但不分化型表达Snail/SIP 1。然后，我们建立了稳定表达Snail和SIP 1的两种分化细胞中的E-cad表达的转染子。在转染子中观察到E-cad表达受到抑制，形态学改变为成纤维细胞样特征，并且侵袭活性显着加速。在一系列与运动和侵袭相关的基因的逆转录-聚合酶链反应中，我们证明了惊人的证据，即基质金属蛋白酶（MMP-1），MMP-2，MMP-7和MT 1-MMP表达强烈上调蜗牛。SIP 1转染组MMP-1、MMP-2和MT 1-MMP表达增强，但增强程度弱于Snail转染组。总之，Snail或SIP 1表达可能在HCC进展过程中被诱导，其中Snail/SIP 1直接抑制E-cad基因转录并通过MMP基因家族的上调激活癌症侵袭。
Loss of E-cadherin (E-cad) triggers invasion, metastasis, and dedifferentiation in various epithelial carcinomas. Recently, it has been reported that two transcription factors, Snail and SIP1 (Smad interacting protein 1), directly repress transcription of the E-cad gene by binding E-box on E-cad promoter. Our aim is to solve the molecular mechanism of Snail and SIP1 in hepatocellular carcinoma (HCC). We first showed an inverse correlation between E-cad and Snail/SIP 1 expression among five HCC lines with different phenotypes. The result indicated that undifferentiated, but not differentiated type expressed Snail/SIP1. Then, we established transfectants stably expressing Snail and SIP1 in two differentiated cells with E-cad expression. Suppressed expression of E-cad, morphologic change into fibroblastoid feature, and remarkable acceleration of invasion activity were observed in the transfectants. In reverse transcription–polymerase chain reaction series of genes relating to motility and invasion, we demonstrated striking evidence that matrix metalloproteinase (MMP-1), MMP-2, MMP-7, and MT1-MMP expressions were strongly upregulated by Snail. On the other hand, MMP-1, MMP-2, and MT1-MMP expressions were enhanced by SIP1 transfection, however, the intensity was weaker than that in Snail transfection. In conclusion, Snail or SIP1 expression may be induced during HCC progression, where Snail/SIP1 directly represses E-cad gene transcription and activates cancer invasion via the upregulation of the MMP gene family.
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影响因子：
5.3
作者：
Carver, EA;Jiang, RL;Gridley, T
通讯作者：
Gridley, T
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Feldmann, G
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Shen, CY
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21.3
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Batlle, E;Sancho, E;de Herreros, AG
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de Herreros, AG